title: The RNA-dependent-RNA polymerase, an emerging antiviral drug target for the Hendra virus.
abstract: Australia is facing a major national medical challenge with the emergence of the Hendra virus (HeV) as a medically and economically important pathogen of humans and animals. Clinical symptoms of human HeV infection can include fever, hypotension, dizziness, encephalitis, respiratory haemorrhage and edema. The window of opportunity for successful patient treatment remains unknown, but is likely to be very narrow. Currently, very few effective therapeutic options are available for the case management of severe HeV infections or the rapid silencing of local outbreaks. This underscores the need for more activity in the drug discovery arena to develop much needed therapeutics that specifically targets this deadly disease. The structural analysis of HeV is very much in its infancy, which leaves many gaps in our understanding of the biology of HeV and makes structure-guided drug design difficult. Structural studies of the viral RNAdependent- RNA polymerase (RdRp), which is the heart of the viral replication machinery, will set the stage for rational drug design and fill a major gap in our understanding of the HeV replication machinery. This review examines the current knowledge based on the multi-domain architecture of the Hendra RdRp and highlights which essential domain functions represent tangible targets for drug development against this deadly disease.
authors.forename: Tony
authors.initials: T
authors.lastname: Velkov
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Carbone
authors.forename: Jesmin
authors.initials: J
authors.lastname: Akter
authors.forename: Sivashangarie
authors.initials: S
authors.lastname: Sivanesan
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Travis
authors.initials: T
authors.lastname: Beddoe
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville 3052, Victoria, Australia. glenn.marsh@csiro.au.
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Marsh
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D045404:Hendra Virus / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D012324:RNA-Dependent RNA Polymerase / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D012324:RNA-Dependent RNA Polymerase